Concurrent use of two dual-combination drenches containing monepantel/abamectin and oxfendazole/levamisole in sheep: effect on marker residues 21 and 28 days after administration.

AIMS: To determine the concentration, in comparison with the maximum residue limit (MRL), of anthelmintic marker residues in the target tissues (liver and fat) of sheep treated concurrently with two oral drenches, one containing monepantel and abamectin and the other oxfendazole and levamisole. METHODS: On day 0 of the study, 12 sheep (six male and six female; 8-9-months old) were dosed according to individual body weight determined the day prior. Zolvix Plus (dual-active oral drench containing 25 g/L monepantel and 2 g/L abamectin) was administered to all animals prior to administration of Scanda (dual-active oral drench containing 80 g/L levamisole hydrochloride and 45.3 g/L oxfendazole). Six sheep (three male and three female) were slaughtered 21 and 28 days after treatment and renal fat and liver samples were collected.Using validated methods, analyses for monepantel sulfone, abamectin, levamisole and oxfendazole (expressed as total fenbendazole sulfone following conversion of the combined concentrations of oxfendazole, fenbendazole and fenbendazole sulfone) were performed on liver samples while renal fat specimens were analysed for monepantel sulfone and abamectin residues only. Detected concentrations were compared to the established MRL in sheep for each analyte determined by the Ministry for Primary Industries. RESULTS: All residues detected in samples of liver and fat collected 21 and 28 days after treatment were below the MRL for each analyte. All liver samples collected on day 21 had detectable monepantel sulfone (mean 232 (min 110, max 388) µg/kg) and oxfendazole (mean 98.7 (min 51.3, max 165) µg/kg) residues below the MRL (5,000 and 500 µg/kg, respectively). Monepantel sulfone (mean 644 (min 242, max 1,119) µg/kg; MRL 7,000 µg/kg) residues were detected in 6/6 renal fat samples. Levamisole residues were detected in 3/6 livers (mean 40.0 (min 14.3, max 78.3) µg/kg; MRL 100 µg/kg), and abamectin residues in 1/6 livers (0.795 µg/kg; MRL 25 µg/kg) and 2/6 fat samples, (mean 0.987 (min 0.514, max 1.46) µg/kg; MRL 50 µg/kg) 21 days after treatment. CONCLUSION AND CLINICAL RELEVANCE: These results suggest that concurrent administration of Zolvix Plus and Scanda to sheep is unlikely to result in an extended residue profile for any of the active ingredients, with all analytes measured being under the approved New Zealand MRL 21 days after treatment. This work was not completed in line with guidance for establishing official residue profiles, nor is it sufficient to propose a new withholding period.

The in vitro response of field strains of sheep blowflies Lucilia sericata and L. cuprina (Calliphoridae) in New Zealand to dicyclanil and triflumuron.

AIM: To evaluate the in vitro efficacy of triflumuron and dicyclanil against field strains of Lucilia sericata and L. cuprina in New Zealand to establish whether anecdotal reports of declining protection periods afforded by dips containing these active ingredients had validity. METHODS: Strains of field-derived blowflies (Lucilia cuprina and L. sericata) were obtained from adult flies from flytraps or larvae from sheep with flystrike submitted from seven regions of the North and two regions of the South Islands of New Zealand. A total of 27 strains of L. sericata and 19 of L. cuprina were established in culture and first instar larvae obtained were exposed in vitro to dilution series of technical-grade dicyclanil (a pyrimidine carbonitrile) and triflumuron (a benzoyl urea). Concentrations lethal to 50% (LC50) and 95% (LC95) of each strain were calculated and tested by probit analysis, with the ratio of LC50 of each strain divided by LC50 of the most susceptible strain (resistance factor) derived in order to facilitate between-strain comparisons of susceptibility. RESULTS: There was considerable variation between strains of L. sericata larvae in their susceptibility to triflumuron, with those least susceptible originating from the Waikato region. Strains from both Tararua and Manawatu regions were most susceptible and East Coast strains intermediate. All strains of the species tested showed a narrow band of susceptibility to dicyclanil with no regional trends apparent. CONCLUSIONS: Representative field-strains of sheep blowflies exhibited a range of susceptibilities to both triflumuron and dicyclanil, suggestive of both genetic heterogeneity among fly populations and the spectrum of dip use in their source areas. This means there should be concerns for the long-term benefits of benzoyl urea insecticides for sheep farmers in New Zealand, but not yet for dicyclanil-based formulations. CLINICAL RELEVANCE: Flystrike is a debilitating and occasionally lethal disease in sheep such that efficacious sheep dips have prophylactic value in reducing the prevalence of the condition.

Managing anthelmintic resistance: is it feasible in New Zealand to delay the emergence of resistance to a new anthelmintic class?

The recent registration in New Zealand of the first new class of broad-spectrum anthelmintic, for use against nematode parasites of ruminants, in nearly three decades has raised the possibility that parasite management practices could be improved to minimise the emergence of resistance to the new drug. A review of knowledge pertaining to the selection of anthelmintic resistance in nematode parasites of sheep highlights a number of management practices which could be altered to achieve this. A number of previously common practices such as whole-flock treatment of adult ewes around lambing, and treatment of lambs as they are moved onto pastures with low parasite contamination have been clearly identified as high risk for selecting resistant parasites. Once high-risk practices have been identified steps can be taken to either eliminate their use or mitigate the associated risk. Much of the focus on the management of resistance around the world is on the retention of susceptible genotypes in refugia. While approaches to retaining unselected parasites are likely to vary around the world, empirical studies indicate that the practice is likely to be effective at slowing the development of resistance. The challenge for farmers and advisors will be to strike a balance between retaining sufficient susceptible parasites to usefully delay the development of resistance while not unduly compromising animal performance and farm profitability. The merits of combining different classes of anthelmintic in order to slow the development of resistance remains somewhat contentious in some countries. However, the attributes of oral anthelmintics are such that they seem likely to meet most, if not all, of the criteria for combinations to be highly effective at slowing the build-up of resistance in nematode parasites. It is evident that considerable progress has been made in understanding the factors involved in selecting anthelmintic-resistant nematodes since the last broad-spectrum anthelmintic class was released in the early 1980s. Therefore, it should be possible to manage a new class of anthelmintic in such a way as to significantly extend its effective life. The challenge is likely to be in convincing farmers of the merits of adopting such pro-active strategies.

A large-scale clinical field study to evaluate the efficacy and safety of an oral formulation of the amino-acetonitrile derivative ( AAD ), monepantel , in sheep in New Zealand.

AIM: To evaluate the efficacy and safety of an oral formulation of the novel anthelmintic, monepantel (AAD 1566), in sheep, in comparison with some other anthelmintics currently registered in New Zealand. METHODS: A study was conducted on 18 farms located throughout the North and South Islands of New Zealand. On each farm, sheep naturally infected with the target nematodes were randomly assigned to groups, which were then treated with either monepantel, at a minimum dose rate of 2.5 mg/kg, or one of five other anthelmintics encompassing the range of single-entity and combination formulations that are commercially available in New Zealand, or left untreated as controls. Faecal samples were collected from all sheep pre-treatment (1-3 weeks before treatment), at the time of treatment, and approximately 1, 2 and 3 weeks after treatment (Days 7, 14 and 21). Faecal nematode egg counts (FEC) were measured in all samples, and the efficacy of treatments, as indicated by reductions in FEC, calculated. All sheep were inspected at least daily, to check for any adverse effects of treatment. RESULTS: On all 18 farms, on Days 7, 14 and 21 (54 test points), the efficacy of the monepantel solution was >95%. At Days 7 and 14 post-treatment, efficacies>99% were recorded in 15 flocks. At Day 21 post-treatment, efficacies>98% were recorded in 13 flocks. Monepantel was as effective, or more effective, than the registered anthelmintics with which it was compared. Moreover, it was effective against strains of nematodes resistant to one or more of the currently available broad-spectrum anthelmintics. The monepantel solution used in this study was well tolerated by the sheep, and no adverse events could be attributed to its use. CONCLUSIONS AND CLINICAL RELEVANCE: When administered as an oral formulation under field conditions, at a minimum dose rate of 2.5 mg/kg, monepantel appeared to be highly effective against all the major genera of gastrointestinal nematodes of sheep, including Haemonchus, Teladorsagia (=Ostertagia), Trichostrongylus, Cooperia, Nematodirus, Chabertia and Oesophagostomum. This included strains resistant to the currently available broad-spectrum anthelmintics. Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep.

Field studies investigating anthelmintic resistance in young cattle on five farms in New Zealand.

AIM: To investigate the efficacy of pour-on anthelmintics against field strains of parasitic nematodes in young cattle on five farms in New Zealand. METHODS: Faecal nematode egg count (FEC) reduction (FECR) tests were carried out on five calf-rearing farms using pour-on formulations of levamisole, ivermectin, eprinomectin, and the simultaneous administration of levamisole and ivermectin. Faecal samples were collected per rectum before treatment and about 7, 14, 21 and 28 days after treatment, for FEC and faecal nematode larval culture. RESULTS: Resistance (i.e. <95% reduction in FEC) of Cooperia oncophora to ivermectin and eprinomectin was identified on all five farms. There was limited evidence of possible emerging resistance in Ostertagia spp to ivermectin but not eprinomectin, in short-tailed larvae of Cooperia spp to ivermectin and eprinomectin, and in Trichostrongylus spp to ivermectin, eprinomectin and levamisole used separately. Levamisole was effective against C. oncophora, but had variable efficacy against Ostertagia spp in the calves in this study. Simultaneous treatment with levamisole and ivermectin pour-on formulations were effective against all genera on all farms. CONCLUSIONS: To effectively manage roundworm parasites in their calves farmers need to be aware of the resistance status of the parasites on their farms. Levamisole is likely to be an effective anthelmintic on most farms at times of the year when the impact of Ostertagia spp is not high. Simultaneous administration of levamisole and ivermectin pour-on anthelmintics to cattle is likely to control both ML-resistant C. oncophora and stages of Ostertagia spp that are not controlled by levamisole alone.